Late dinner impairs glucose tolerance in MTNR1B risk allele carriers: A randomized, cross-over study

Jesus Lopez-Minguez, Richa Saxena, Cristina Bandín, Frank A Scheer, Marta Garaulet, Jesus Lopez-Minguez, Richa Saxena, Cristina Bandín, Frank A Scheer, Marta Garaulet

Abstract

Background & aims: Late-night dinner eating is associated with increased risk for type-2 diabetes. The underlying mechanism is unclear. One explanatory hypothesis is that the concurrence of elevated circulating melatonin and high glucose concentrations (characterizing late eating) leads to impaired glucose tolerance. However, to date no study has tested the influence of physiological melatonin concentrations on glucose-tolerance. The discovery of melatonin receptor MTNR1B as a diabetes risk gene provides evidence for a role of physiological levels of melatonin in glucose control. The aim of our study was to test the hypothesis that elevated endogenous melatonin concentrations worsen glucose control when eating late. Registered under ClinicalTrials.gov Identifier no. NCT03003936.

Methods: We performed a randomized, cross-over trial to compare glucose tolerance in the presence (late dinner) or absence (early dinner) of elevated physiological melatonin concentrations and we compared the results between homozygous carriers and non-carriers of the MTNR1B risk allele.

Results: The concurrence of meal timing with elevated endogenous melatonin concentrations resulted in impaired glucose tolerance. This effect was stronger in MTNR1B risk-carriers than in non-carriers. Furthermore, eating late significantly impaired glucose tolerance only in risk-carriers and not in the non-risk carriers.

Conclusions: The interaction of dinner timing with MTNR1B supports a causal role of endogenous melatonin in the impairment of glucose tolerance. These results suggest that moving the dinner to an earlier time may result in better glucose tolerance specially in MTNR1B carriers.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT03003936.

Keywords: Diabetes; Glucose tolerance; MTNR1B; Meal timing; Melatonin.

Conflict of interest statement

Conflict of interest statement

The authors declare no competing financial interests

Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Figures

Figure 1. Experimental protocol
Figure 1. Experimental protocol
Example of a typical protocol based on each individual´s habitual bedtime for EE and LE conditions is represented in this figure. In both conditions the subject ate the same food for breakfast, lunch and dinner, only the time of the food intake was modified between the two conditions. Just before the dinner, measurements of glucose, light intensity and saliva were collected. Light intensity and glucose were also measurements at 30, 60, 90 and 120 minutes after the start time for dinner, and saliva samples were also collected at 60 and 120 minutes after dinner. From at least 30 minutes before until 2 hours after the start of the test dinner, subjects were under moderately bright light conditions for the early eating condition, under low light conditions for the late eating condition.
Figure 2. Glucose tolerance curve for total…
Figure 2. Glucose tolerance curve for total population and risk carriers and non-carriers of the MTNR1B gene
Each curve represents the glucose concentrations just before dinner (T0) and 30, 60, 90 and 120 minutes after dinner. The black line is for the late diner condition (LE) and the gray line is for the early dinner condition (EE). Glucose profiles for the total population are represented in the panel 1A, while glucose profiles for the two MTNR1B genotypes, risk carriers (GG) and non-carriers (CC), are represented in the panels 2B and 2C, respectively.

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